Z-msthoxy-j-chloso-g-methyl



3,136,205 Patented Apr. 21, 1964 2-METHOXY-3@QLQRQdt EETHYL BENZGEC BEER/A313 ES Sidney B. Richter, Chicago, Ill assignor to Velsicol Chemical Corporation, Chicago, iii, a corporation of Illinois No Eran-hag. Filed Early 26, 1961, Ser. No. 125,391 13 Ciairns. (Cl. 260-3 14) This invention relates to new herbicidal compositions of matter. More specifically, this invention relates to the control of undesirable plant life with 2-methoxy-3-chloromethylbenzoic acid, its anhydride, its amides, its esters, its alkali metal salts, or its amine salts. 2-methoxy-3- chloro-6-rnethyl'oenzoic acid, which has the structure H O OCH;

will hereinafter be referred to as compound I. This chemical compound and its derivatives as cited above have marked activity as herbicides useful for the control of undesirable plant life.

Compound I can be obtained readily, for example, from the known compound 2-chloro-5-methylphenol. A carboxyl group is first introduced into the ortho position to the hydroxy group by treating the phenol under superatmospheric pressure with carbon dioxide gas in the presence of a base such as potassium carbonate. The reaction is suitably carried out in a bomb winch is constructed to withstand superatrnospheric pressures. The exact pressure to be used is not critical, but initial pressures in the range from about 500 to 1000 pounds per square inch are preferred. Similarly, the reaction temperature is not crtiical, but temperatures in the range from about 100 to 200 C. are preferred. The reaction is generally complete within 24 hours, fit er which time the bomb is cooled. The reaction mixture is washed out with water and acidified with a dilute acid such as hydrochloric acid to precipitate the desired 3-..hloro-6- methylsalicylic acid, which is then filtered 05 and dried. The product so obtained is ordinarily pure enough to be used directly in the second step in the synthesis.

The 3-chloro-6-methylsalicylic acid is then treated with dimethyl sulfate in basic medium in a suitable solvent such as acetone to convert it to the desired methyl ether. Suitable bases are such substances as sodium hYdIOXldfi or potassium carbonate. About equimolecular proportions of the salicylic acid and base can be used, but it is desirable to use an excess or" the dimethyl sulfate. The reaction mixture is preferably heated at reflux temperature to complete the reaction. The product is then heated with an aqueous solution of a base such as sodium hydroxide to hydrolyze any carboxylic acid ester which may have formed. The cooled reaction mixture is acidified with a mineral acid such as hydrochloric acid; and the precipitated solid is filtered, washed with cold water, and dried to give compound I. \Vhile the compound I obtained in this manner is suitable for many herbicidal uses as such, if desired it can be purified, as by recrystallization from a suitable solvent.

The anhydride of compound I is prepared by the removal of one molecule of water from two molecules of compound I as the free acid. In practice, it is convenient to prepare the anhydride by the acylation of the free carboxylic acid by its acid halide in the presence of a strong acylating agent such as pyridine. Thus, a mixture of dry pyridine and dry benzene is treated with 1 mole of the acid chloride of compound I. The slightly exothermic reaction proceeds with the formation of an intermediate pyridinium salt. One mole of compound I as the free acid is then added, the precipitate of pyridine hydrochloride is removed, and the anhydride of compound I is isolated by removal of the benzene.

The acid halide of compound I required in the above and other syntheses is prepared by the reaction of the free acid with a phosphorus trihalide in the conventional manner. Thus, the treatment of compound I with phosphorus trichloride until the reaction ceases produces the acid chloride of compound I.

Compounds which are salts, esters, or amides of compound I can be prepared readily from the free acid. Thus, treatment of the free acid with ammonium hydroxide gives a product which is the salt ammonium 2-methx -3-chloro-6-methylbenzoate. Similarly, an alkali metal salt of compound I can be made by the treatment of the free acid with bases, such as the hydrorddes, of alkali metals. Treatment of the acid with sodium hydroxide thus gives the salt sodium 2-methoxy-3-chloro-6-methylbenzoate as the product, while the use of potassium hydroxide gives the salt potassium 2-methoxy-3-chloro6- methylbenzoate.

Amine salts of compound I are prepared by the addition of the free acid to v rious amines. Typical amines which can be used to prepare such amine salts are dimethylamine, trimethylau ine, triethylamine, diethanolamine, triethanolarnine, isopropylamine, morpholine, and the like. The resulting products are, respectively, the dimethylamine, trimethylamine, triethylamine, diethanolamine, triethanolamine, isopropylarnine, and morpholine salts of 2-methoxy-3-chloro6-methylbenzoic acid.

Esters of compound I are prepared by the condensation of the acid with various alcohols. Thus, the condensation of methyl alcohol with compound I gives the desired ester, meth l 2 methoxy 3 chloro-6-methylbenzoate. (Ether typical alcohols which can be used are propyl, iso propyl, n-butyl, sec-butyl, isobutyl, tert-butyl, amyl, hexyl, heptyl, octyl, nonyl, decyl, and the like. The products are the corresponding alkyl esters of 2-rnethoxy-3- chloro--methyl enzoic acid. Although such complex esters as those prepared by the esterification of compound I with butoxyethanol, propylene glycol butyl ether, tertoctyl alcohol, 3-(2-butoxyethoxy)-propyl alcohol, tetrahydroturfuryl alcohol, and the like are useful products in accordance with this invention, preferred esters are those in which the esterifying group is an unsubstituted alkyl group which contains from 1 to 10 carbon atoms. The condensation of the acid with the alcohol is carried out suitably in an inert solvent such as an aromatic hydrocarbon and in the presence of a few percent by Weight of an acid catalyst such as p-toluene-sulfonic acid. The water which forms during the esterification reaction can be removed continuously in many cases from the reaction mixture by distillation as it forms, and its volume can be measured to determine when the esterification is complete. The ester is then isolated by distillation of the inert solvent.

Amides of compound I can be prepared conveniently by the reaction of the acid halide of compound I with armmonia or various amines. The reaction can be carried out in an inert solvent such as ether or benzene. Preferably two moles of the amine are used for each mole of the acid halide employed, since the hydrogen halide released during the reaction is taken up by some of the free amine which remains. The simplest amide, Z-methoxy- 3-chloro-6-methylbenzamide, can be prepared by the reaction of the acid chloride of compound I with ammonia, either as the free gas or as an aqueous solution. This amide can also be prepared by hydrolysis of the corresponding nitrile. Substituted amides are prepared by the reaction of the acid halide of compound I with amines such as any of the primary or secondary amines suggested above for the preparation of the amine salts of compound I. Thus, for example, the reaction of the acid chloride of compound I with methylamine, butylamine, decylamine, or diethylamine gives the N-methyl-, N-butyl-, N -decyl, or N,N-diethyl-2-methoxy-3-chloro-6-n1ethylbenzamides, respectively. While more complex amines such as the aromatic amines can be used as the amine reactant to give desirable products, which specifically named as anilides, preferred amine reactants are alkylamines containing up to 10 carbon atoms.

For practical use as herbicides, the compounds of this invention are formulated with inert carriers to obtain proper concentrations and to facilitate handling. For example, these compounds can be formulated into dusts by combining them with such inert substances as talcs or clays. The alkali metal salts of compound I are particularly suited to such dust formulations, and dusts containing from 5 to 25 percent by weight of active compound are convenient for use in the field. The compounds of this invention, however, are preferably applied as sprays. These can be made as simple solutions by dissolving the compounds in organic solvents such as xylene, kerosene, or the methylated naphthalenes. The esters of compound I, which ordinarily are liquids at room temperature, are particularly suited to formulation by this method. The amine salts of compound I often show good solubility in water and can be used directly as aqueous solutions.

The compounds of this invention can also be emulsified or suspended in water by the addition of emulsifiers and wetting agents. The formulations of these active herbicidal compounds are either applied directly to the plants to be controlled, or the soil in which the plants are growing can be treated. Substances such as other pesticides, stabilizers, activators, synergists, spreaders and adhesives can be added to the formulations if desired. There is no significant diflerence in effect from the amount of water or organic solvent for diluting these herbicides, providing the same amount of chemical is distributed evenly over a given area. Such distribution can be obtained, for example, with low-pressure, low-volume sprays at the rate of about gallons of spray per acre.

In applying the herbicidal compounds, consideration must be given to the nature and stage of growth of the crop, the species of weeds present, the stage of growth of the weeds, environmental factors influencing the rate and vigor of the weed growth, weather conditions at the time of application and immediately following, and the dosage to be applied to a given area. Weeds are most susceptible when they are small and growing rapidly. Early application, therefore, results in better control with less chemical and increased yields because of the early destruction of the competing weeds. The larger and older the weeds the higher the concentration needed to kill them. Summer annuals such as lambs-quarters, pigweeds, cocklebur, and sunflower should be sprayed when they are less than 4 inches high. Winter annuals such as various mustards, fan-weed, yellow star-thistle, and wild radish are most easily killed While they are still in the rosette stage. Usually weeds growing rapidly under optimum conditions are relatively susceptible, whereas those growing under adverse conditions tend to be resistant to the herbicide sprays.

The effectiveness of the compounds of this invention in small quantities makes them economically sound for weed control on large areas, with a great saving in labor and cost, in addition to corresponding crop increases. These compounds are particularly valuable in weed control because they are harmful to many weeds but harmless or relatively harmless to some cultivated crops. Minute quantities in contact with plant tissues may be absorbed and translocated to all parts of the plant, causing striking changes in the form and functions and often resulting in their death. The actual amount of compound to be used depends on a variety of factors but is influenced more pounds of compound I or its derivatives per acre for good control. Dosage adjustments with the lowvolume, low-pressure applications suggested can be made by changing the nozzle size, nozzle spacing, pressure, or traveling. rate of the spray equipment.

The manner in which the herbicidal compounds of this invention can be prepared and utilized is illustrated in the following examples:

EXAMPLE 1 Preparation of 3-Chl0r0-6-Methylsalicylic Acid A mixture of 2-chloro-5-methylphenol (25 g.; 0.175 mole) and anhydrous potassium carbonate (60 g.) was ground and placed with g. of clay saddles in a steel bomb, which was then pressured to 600 psi. with carbon dioxide gas. After 26 hours of heating at C., when the pressure had dropped to 0, the bomb was cooled and opened. The contents of the bomb were treated with 250 ml. of water; and the solid was filtered off and washed twice with ether. The solid (with clay saddles) was acidified with hydrochloric acid, diluted with 150 ml. of water, treated with sodium bicarbonate, and heated to dissolve the sodium salt which formed. The solution was filtered, cooled, and acidified with hydrochloric acid. The precipitate was filtered with suction and dried to give 26.2 g. (81% of theory) of 3-chloro-6-methylsalicylic acid, melting point l74176 C.

EXAMPLE 2 Preparation of 2-Methoxy-3-Chl0r0-6-Methylbenz0ic Acid (COMIPOUND I) 3-ch1oro-6-methylsalicylic acid (27.9 g.; 0.15 mole) is ground with anhydrous potassium carbonate (20.7 g.; 0.15 mole) and added with stirring to 250 ml. of acetone in a 500-ml., 3-necked, round-bottomed flask fitted with a mechanical stirrer, reflux condenser, internal thermometer, and addition funnel. The mixture is heated to reflux temperature, and dimethyl sulfate (37.8 g.; 0.30 mole) is added dropwise with stirring over a period of about 15 minutes. The reaction mixture is then stirred and refluxed overnight, cooled, and filtered. The solvent is evaporated from the filtrate, and the residue is placed with 10 g. of sodium hydroxide dissolved in 400 ml. of water in a Preparation of the Sodium Salt 0 Compound I Compound'I (0.5 mole) is dissolved in 500 cc. of methanol and treated with a solution of sodium hydroxide The mixture is stirred and (20 g.; 0.5 mole) in 100 cc. of methanol. The methanol 1 is removed by distillation in vacuo on the steam bath, and the solid residue is slurried with 100 cc. of cold, dry

ether, filtered, pressed dry, and dried completely in a vacuum oven to give the desired sodium salt of compound I.

EWPLE 4 Preparation of the Ammonium Salt of Compound I Treatment of Compound I (0.5 mole) in 500 cc. of methanol with 34 cc. of commercial concentrated ammonium hydroxide according to the method given in the previous example gives the desired ammonium salt of Compound I.

EXAMPLE 5 Preparation of the Dimethylamine Salt of Compound I Compound I (0.5 mole) is dissolved in 500 cc. of dry ether and treated with dimethylarnine (22.5 g. 0.5 mole). The solid which separates is filtered, washed twice with 100 cc. portions of cold ether, filtered, pressed dry, and dried completely in a vacuum oven to give the desired dimethylarnine salt of Compound 1.

EXAMPLE 6 Preparation of the Diethanolamine Salt of Compound I In the manner described in the previous example, Compound I (0.5 mole) is treated with diethanolamine (52.5 g.; 0.5 mole) in 500 cc. of dry ether. The product which is isolated is the diethanolarnine salt of Compound I.

EXAMPLE 7 Preparation of the Morpholine Salt of Compound 1 Compound I (0.5 mole) is treated with morpholine (43.5 g.; 0.5 mole) in 500 cc. of ether, and the product is worked up as described for the preparation of the dimethylamine salt to give the desired morpholine salt of Compound I.

EXAMPLE 8 Preparation of the Ethyl Ester of Compound 1 Compound I (0.5 mole), ethyl alcohol (23 g.; 0.5 mole), and 3.0 g. of p-toluenesulfonic acid are dissolved in 500 ml. of benzene, and the solution is placed in a 1-liter, round-bottomed flask fitted with a reflux condenser and a calibrated Dean-Stark tube. The solution is heated at reflux temperature until 9 cc. of Water have been collected in the Dean-Stark tube. The cooled reaction mixture is then extracted twice with 50-cc. portions of 10% sodium carbonate solution, and filtered. These benzene is distilled off in vacuo on the steam bath, and the residue is then distilled in vacuo to give the desired ethyl ester of Compound I.

EXAMPLE 9 Preparation of the Decyl Ester of Compound I In the manner and apparatus described in the previous example, Compound I (0.5 mole) and normal primary decyl alcohol (79 g.; 0.5 mole) are refluxed in 500 ml. of benzene in the presence of 3.0 g. of p-toluenesulfonic acid until 9 cc. of Water have been distilled from the reaction mixture. Worl -up of the reaction mixture as described in the previous example gives the desired decyl ester of Compound I.

EXAMPLE 10 Preparation of the n-Butyl Ester of Compound 1 The reaction of Compound I (0.5 mole) and n-butyl alcohol (37 g.; 0.5 mole) by the method described above for the preparation of the ethyl ester is used to prepare the n-butyl ester of Compound 1.

EXAMPLE 11 Preparation of the Acid Chloride of Compound I Compound I (1 mole) is placed with 500 cc. of dry benzene in a 2-liter, 3-necked, round-bottomed fiaslr fitted with a mechanical stirrer, reflux condenser (calcium chloride tube), and dropping tunnel. Phosphorus trichloride (123 g.; 0.9 mole) is added slowly dropwise with vigorous stirring while the reaction flask is cooled with cold Water if necessary to control the reaction. When all the R31 has been added and the evolution of hydrogen chloride has ceased, the reaction mixture is then transferred to distillation apparatus, and the solvent is distilled off. The residue is then distilled in vacuo to give the desired acid chloride of Compound I.

EXAMPLE 12 Preparation of the Amide of Compound 1 One mole of the acid chloride of Compound I is placed with 500 cc. of dry benzene in a 1-liter, 3-neckcd flask fitted with a reflux condenser, mechanical stirrer, and a gas inlet tube having a sparger tip. The mixtin'e is stirred While dry ammonia gas is passed into the mixture for several hours. When the ammonia gas is no longer taken up, the precipitated salt is filtered 0E and extracted twice with ml. portions of ether. The ether extracts and benzene filtrate are dried over magnesium sulfate and filtered, and the solvents are distilled oil to give the desired amide of Compound I.

EXAMPLE 13 Preparation of the N-n-Decylamide of Compound I One mole of the acid chloride of Compound I and 500 ml. of dry benzene are placed in a 2-liter, S-necked, roundbottomed flask fitted with a mechanical stirrer, refiux condenser, internal thermometer, and dropping funnel. n-Decylamine (314 g.; 2.0 moles) in 250 ml. benzene is added drop-Wise with vigorous stirring. When all the amine has been added, the reaction mixture is reiiuxed for 2 hours and cooled, after which the precipitated salt is filtered off and extracted With two 100 ml. portions of ether. The ether extracts and benzene filtrate are dried over magnesium sulfate and filtered. Distillation of the solvents gives the desired N-n-decylamide of Compound I.

EXAMPLE 14 Preparation of the NJV-Diethylamide of Compound I One mole of the acid chloride of Compound I is treated with diethylamine (146 g.; 2.0 moles) in the manner and apparatus described in the previous example to give the N,N-diethylamide of Compound I.

EXAMPLE 15 Preparation of the Anhydride of Compound I Dry pyridine (158 g.; 2.0 moles) and 1 liter of dry benzene are placed in a 2-liter, 3-necked, round-bottomed flask fitted with a dropping funnel, mechanical stirrer, reflux condenser, and internal thermometer. One mole of the acid chloride of compound I, which is prepared as described in a previous example, is added rapidly with stirring to the reaction mixture. Compound I (1 mole) is then added in portions over a period of about 10 minutes with rapid stirring. The pyridine hydrochloride which precipitates is filtered off, and the benzene is distilled from the filtrate in vacuo. The residue contains the desired anhydride of compound I, which can be purified by recrystallization from a suitable solvent.

EXAMPLE 16 Preparation 0 an Emulsifiable Concentrate of Compound I The following concentrate is prepared by mixing the ingredients intimately in the given percentage proportions by weigi t:

Percent Compound I 25 Antarox A-400 4O Methanol 35 Antarox A-400 is the trade name under which a nonionic detergent of the aromatic polyethylene glycol ether type is sold. The above concentrate is diluted with water to the desired concentration for use.

EXAMPLE 17 Preparation of an Emulsifiable Concentrate of the n-Bzttyl Ester of Compound I The following ingredients are mixed thoroughly in the given percentage proportions by weight:

, Percent n-Butyl ester of compound I a- 59 Xylene 10 Triton X-100 5 Kerosene 26 Triton X-100 is the trade name under which an emulsifier of the alkyl aryl polyether alcohol type is sold. The above concentrate is diluted with water to the desired concentration for use.

EXAMPLE 18 Preparation a Dust from the Sodium Salt of Compound I The sodium salt of compound I (10% by weight) and talc (90% by weight) are combined and ground to the desired particle size in a mechanical grinder-blender.

The herbicidal activity of chemical compounds is often demonstrated by the ability of the chemicals to kill or arrest the growth of tomato plants. The tomato plant is readily grown and maintained under uniform conditions for experimental purposes in greenhouses, and its response to chemicals is very similar to that observed for a wide variety of economically important species of undesirable plant life in the field.

The herbicidal activity of the compounds of this invention, for example, can be demonstrated in greenhouse experiments on young potted tomato plants (Bonny Best variety). The compounds are formulated into 10 percent Wettable powders and are dispersed in water at a concentration of 2,000 parts per million actual chemical. Ten milliliters of an aliquot portion of the dispersion is added to the soil surface of the tomato plants, approximately to 7 inches tall. In order to avoid undue concentration or accumulation of the chemical in any given area, 5 holes the size of a pencil and about 1 inch deep are punched in the soil surface around the shoot, and the milliliter application is divided equally among the 5 holes. Three plants are used for each application. The treated plantsare held under greenhouse conditions for 7 days, provided with subterranean Watering, and observed for response to treatment. The results indicate a high order of herbicidal toxicity of the compounds of this invention. Tests carried out on such actual Weed species as French Weed, pigweed, crabgrass, yellow foxtail, ryegrass, chickweed and white cockle also indicate the marked herbicidal activity of these new compounds.

This application is a continuation-in-part of my application Serial No. 804,598, filed April 7, 1959, now abandoned.

I claim:

1. A compound selected from the group consisting of 2-methoxy-3-chloro-6-methylbenzoic acid, its anhydride, its alkali metal salts, its ammonium salt, its morpholine salt, its alkyl amine salts in which the amine component is an unsubstituted alkyl amine of up to six carbon atoms, its alkanol amine salts in which the amine component is an unsubstituted alkanol amine of up to six carbon atoms, its esters in which the esterifying group is an unsubstituted alkyl group of from one to ten carbon atoms, its butoxyethanol ester, its tetrahydrofurfuryl alcohol ester, its un- V substituted amide, and its alkyl amides in which the amine component is an unsubstituted alkyl amine of up to ten carbon atoms.

2. An alkali metal salt of 2-methoxy-3-ch1oro-6-methylbenzoic acid.

3. An alkyl amine salt of 2-methoxy-3-chloro-6-methylbenzoic acid in which the amine component is an unsubstituted alkyl amine of up to six carbon atoms.

4. An alkanol amine salt of 2-methoxy-3-chloro-6methylbenzoic acid in which the amine component is an unsubstituted alkanol amine of up to six carbon atoms.

5. An ester of 2-methoxy-3-chloro-6-methylbenzoic acid in which the esterifying group is an unsubstituted alkyl group of from one to ten carbon atoms.

6. An alkyl amide of 2-methoxy-3-chloro-6-methylbenzoic acid in which the amine component is an unsubstituted alkyl amine of up to ten carbon atoms.

7. 2-methoxy-3-chloro-6-methylbenzoic acid.

8. Sodium 2-methoxy-3-chloro-6-methylbenzoate.

9. The diethanolamine salt of Z-methoxy-3-chloro-6- methylbenzoic acid.

10. n-Butyl 2-methoxy-3-chloro-6-methylbenzoate.

11. bis (2-methoxy-3-chloro-6-methylbenzoic) anhydride.

12. The dimethylarnine salt of 2-methoxy-3-chloro-6- methylbenzoic acid.

13. The tetrahydrofurfuryl alcohol ester of Z-methoxy- 3-chloro-6-methylbenzoic acid.

References Cited in the file of this patent UNITED STATES PATENTS Pfaff et a1 Sept. 25, 1934 Searle July 15, 1959 Richter Dec. 12, 1961 OTHER REFERENCES volume 8A 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF 2-METHOXY-3-CHLORO-6-METHYLBENZOIC ACID, ITS ANHYDRIDE, ITS ALKALI METAL SALTS, ITS AMMONIUM SALT, ITS MORPHOLINE SALT, ITS ALKYL AMINE SALTS IN WHICH THE AMINE COMPONENT IS AN UNSUBSTITUTED ALKYL AMINE OF UP TO SIX CARBON ATOMS, ITS ALKANOL AMINE SALTS IN WHICH THE AMINE COMPONENT IS AN UNSUBSTITUTED ALKANOL AMINE OF UP TO SIX CARBON ATOMS, ITS ESTERS IN WHICH THE ESTERIFYING GROUP IS AN UNSUBSTITUTED ALKYL GROUP OF FROM ONE TO TEN CARBON ATOMS, ITS BUTOXYETHANOL ESTER, ITS TETRAHYDROFURFURYL ALCOHOL ESTER, ITS UNSUBSTITUTED AMIDE, AND ITS ALKYL AMIDES IN WHICH THE AMINE COMPONENT IS AN UNSUBSTITUTED ALKYL AMINE OF UP TO TEN CARBON ATOMS.
 13. THE TETRAHYDROFURFURYL ALCOHOL ESTER OF 2-METHOXY3-CHLORO-6-METHYLBENZOIC ACID. 